Borna disease is an immune-mediated neurologic syndrome {Narayan, O., et al., Science 220:1401-1403 (1983)} caused by infection with Borna disease virus (BDV). BDV is a neurotropic, nonsegmented and negative-strand RNA virus that causes a progressive, immune-mediated neurologic disease characterized by disturbances in movement and behavior {Ludwig, H., et al., Prog. Med. Virol, 35:107-151}. It causes fatal disease in expensive domestic animals. Although natural infection was originally considered to be restricted to horses and sheep in Southeastern Germany, recent studies suggest that BDV infects horses in North America {Kao, M., et al., Vet.Rec., 132:241-4 (1993)}, cats in Sweden {Lundgren, A.-L., et al., Zbl. Vet. Med. [B], 40:298-303 (1993)}, ostriches in Israel (Malkinson, M., et al., Vet. Rec., 133:304 (1993)) and some human subjects with neuropsychiatric disorders in Europe and North America {Bode, L., et al., Arch. Virol. [Suppl], 7:159-167 (1993); Bode, L., et al., Lancet, ii:689 (1988); Fu, Z. F., et al., J. Affect. Disorders, 27:61-68 (1993) and Rott, R., et al., Science, 228:755-756 (1985)}.
Experimental infection in rats (Narayan, O., et al., Science, 220:1401-1403 (1983)) results in a multiphasic syndrome characterized by hyperactivity, stereotyped behaviors, dyskinesias and dystonias.
Though natural infection has not been reported in primates, subhuman primates can be infected experimentally {Sprankel, H., et al., Med. Microbiol. Immunol. 165:1-18 (1978) and Stitz, L., et al., J. Med. Virol. 6:333-340 (1980)}. Antibodies to BDV proteins have been found in patients with neuropsychiatric disorders (Rott, R., et al., Science 228:755-756 (1985); Fu, Z. F., et al., J. Affective Disord. 27:61-68 (1993) and Bode, L., et al., Arch. Virol. (Suppl.) 7:159-167 (1993)).
Because BDV grows only to low titer, it was difficult to purify for analysis. However, the identification of BDV cDNA clones by subtractive hybridization (Lipkin, W. I., et al., Proc. Natl. Acad. Sci. USA 87:4184-4188 (1990) and VandeWoude, S., et al., Science 250:1276-1281 (1990)) and, more recently, the advent of a method for isolation of virus particles {Briese, T., et al., Proc. Natl. Acad. Sci. USA 89:11486-11489 (1992)} led to partial characterization of BDV as a negative-strand RNA virus which transcribes its RNA in the cell nucleus {Briese, T., et al., Proc. Natl. Acad. Sci. USA 89:11486-11489 (1992)}.
The diagnosis of BDV infection is based on the appearance of a clinical syndrome consistent with disease, and the presence of serum antibodies that detect viral proteins in infected cells by indirect immnunofluorescent test (IFT) (Pauli, G., et al., Zbl. Vet. Med. [B] 31:552-557 (1984)), Western blot (WB; immunoblotting) or immunoprecipitation (IP) (Ludwig, H., et al., Prog. Med. Virol, 35:107-151 (1988)). These methods are cumbersome and difficult to use for large surveys of human and livestock populations.